The adiponectin paralog CORS‐26 has anti‐inflammatory properties and is produced by human monocytic cells

Weigert, Johanna; Neumeier, Markus; Schäffler, Andréas; Fleck, Martin; Schölmerich, Jürgen; Schütz, Christian; Buechler, Christa

doi:10.1016/j.febslet.2005.09.022

Cited by 84 publications

(80 citation statements)

References 16 publications

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“…Previous in vitro studies have shown that CTRP3 (also known as CORS26/cartducin) (18) stimulates chondrogenic precursor cell proliferation (19), promotes angiogenesis (20), and is overexpressed in the osteosarcoma cell line (21). In primary monocytes derived from healthy but not type 2 diabetic humans, recombinant human CTRP3 reduces proinflammatory cytokine IL-6 and TNF-␣ secretion in response to lipopolysaccharide stimulation, suggesting an anti-inflammatory role (22). Beyond these in vitro studies, the biological relevance and function of CTRP3 in vivo remain unknown.…”

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confidence: 99%

C1q/TNF-related Protein-3 (CTRP3), a Novel Adipokine That Regulates Hepatic Glucose Output

Peterson

Wei

Wong

2010

Journal of Biological Chemistry

218

274

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Adipose tissue-derived adipokines play important roles in controlling systemic insulin sensitivity and energy balance. Our recent efforts to identify novel metabolic mediators produced by adipose tissue have led to the discovery of a highly conserved family of secreted proteins, designated as C1q/TNFrelated proteins 1-10 (CTRP1 to -10). However, physiological functions regulated by CTRPs are largely unknown. Here we provide the first in vivo functional characterization of CTRP3. We show that circulating levels of CTRP3 are inversely correlated with leptin levels; CTRP3 increases with fasting, decreases in diet-induced obese mice with high leptin levels, and increases in leptin-deficient ob/ob mice. A modest 3-fold elevation of plasma CTRP3 levels by recombinant protein administration is sufficient to lower glucose levels in normal and insulin-resistant ob/ob mice, without altering insulin or adiponectin levels. The glucose-lowering effect in mice is linked to activation of the Akt signaling pathway in liver and a marked suppression of hepatic gluconeogenic gene expression. Consistent with its effects in mice, CTRP3 acts directly and independently of insulin to regulate gluconeogenesis in cultured hepatocytes. In humans, alternative splicing generates two circulating CTRP3 isoforms differing in size and glycosylation pattern. The two human proteins form hetero-oligomers, an association that does not require interdisulfide bond formation and appears to protect the longer isoform from proteolytic cleavage. Recombinant human CTRP3 also reduces glucose output in hepatocytes by suppressing gluconeogenic enzyme expression. This study provides the first functional evidence linking CTRP3 to hepatic glucose metabolism and establishes CTRP3 as a novel adipokine.As the largest endocrine organ, adipose tissue secretes many bioactive molecules that circulate in blood, collectively termed adipokines (1). These proteins include leptin, adiponectin, resistin, retinol-binding protein 4 (RBP4), omentin, and vaspin (2-7). Adipokines play important roles in energy homeostasis; their circulating levels are often dysregulated in conditions of obesity and/or diabetes (1). Adiponectin, the most highly expressed and intensely studied adipokine, has insulin-sensitizing, anti-inflammatory, and antiatherogenic properties (8). Allelic polymorphisms and reduced plasma adiponectin levels are tightly linked to insulin resistance and type 2 diabetes (8). A large body of evidence implicates adiponectin as a major insulin-sensitizing adipokine as well as an important biomarker and therapeutic target for obesity-associated metabolic diseases (1, 8). However, variable and relatively mild metabolic dysfunctions in adiponectin knock-out mice suggest the existence of additional metabolic regulators sharing overlapping function with adiponectin (9 -12). Our efforts to identify such mediators produced by adipose tissue have led to the discovery of a highly conserved family of secreted proteins, designated as C1q/TNF-related proteins 1-10 (CTRP1 to -10) (...

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confidence: 99%

C1q/TNF-related Protein-3 (CTRP3), a Novel Adipokine That Regulates Hepatic Glucose Output

Peterson

Wei

Wong

2010

Journal of Biological Chemistry

218

274

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“…In this context, it is important to note that human CORS-26 mRNA is up-regulated in osteosarcoma cells. These data also indicate a role for CORS-26 in the context of mesenchymal tissue development and in the pathogenesis of bone and skeletal diseases 6 . Akiyama et al 7 have reported that stimulation of osteosarcoma cells by CORS-26 promotes tumor cell growth but not migration in vitro.…”

Section: Cors-26 In the Regulation Of Osteosarcoma Cellsmentioning

confidence: 84%

“…Whereas adiponectin is exclusively expressed by adipocytes, CORS-26 mRNA is also detected in cartilage, kidney, colon, small intestine, placenta, lung, spleen, fibroblasts, human monocytic and dendritic cells 5,6 . In addition, strong CORS-26 mRNA expression has been found in osteosarcoma, chondroblastoma and giant cell tumors 2,3,6 . …”

Section: Cors-26 Expressionmentioning

confidence: 99%

“…CORS-26 expression was assessed using hybridization (a method with lower sensitivity) and RT-PCR techniques where CORS-26 mRNA was easily amplified from total RNA isolated from cells (monocytes) 5,6 .…”

Section: Cors-26 Gene Expressionmentioning

confidence: 99%

“…The human homolog of the mouse CORS-26 gene has also been identified and mapped to the chromosome locus 5p13.2-13.1 which is close to the locus of the growth hormone receptor (GHR) gene (5p13. [1][2][3][4][5][6][7][8][9][10][11][12] 2,3,5 .…”

Section: Introductionmentioning

confidence: 99%

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COLLAGENOUS REPEAT-CONTAINING SEQUENCE OF 26 kDa PROTEIN - A NEWLY DISCOVERED ADIPOKINE - SENSU LATO - A MINIREVIEW

Švesták¹,

Sporová²,

Hejduk³

et al. 2010

BIOMED PAP

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C1q/TNF‐Related Protein 3 (CTRP3) Function and Regulation

Liu

Wright

Peterson

2017

Comprehensive Physiology

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As the largest endocrine organ, adipose tissue secretes many bioactive molecules that circulate in blood, collectively termed adipokines. Efforts to identify such metabolic regulators have led to the discovery of a family of secreted proteins, designated as C1q tumor necrosis factor (TNF)-related proteins (CTRPs). The CTRP proteins, adiponectin, TNF-alpha, as well as other proteins with the distinct C1q domain are collectively grouped together as the C1q/TNF superfamily. Reflecting profound biological potency, the initial characterization of these adipose tissue-derived CTRP factors finds wide-ranging effects upon metabolism, inflammation, and survival-signaling in multiple tissue types. CTRP3 (also known as CORS26, cartducin, or cartonectin) is a unique member of this adipokine family. In this review we provide a comprehensive overview of the research concerning the expression, regulation, and physiological function of CTRP3.

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The adiponectin paralog CORS‐26 has anti‐inflammatory properties and is produced by human monocytic cells

Cited by 84 publications

References 16 publications

C1q/TNF-related Protein-3 (CTRP3), a Novel Adipokine That Regulates Hepatic Glucose Output

C1q/TNF-related Protein-3 (CTRP3), a Novel Adipokine That Regulates Hepatic Glucose Output

COLLAGENOUS REPEAT-CONTAINING SEQUENCE OF 26 kDa PROTEIN - A NEWLY DISCOVERED ADIPOKINE - SENSU LATO - A MINIREVIEW

C1q/TNF‐Related Protein 3 (CTRP3) Function and Regulation

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